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dc.contributor.advisorJohnston, Keith P., 1955-en
dc.contributor.advisorWilliams, Robert O., 1956-en
dc.creatorChen, Xiaoxiaen
dc.date.accessioned2008-08-28T21:49:23Zen
dc.date.available2008-08-28T21:49:23Zen
dc.date.issued2004en
dc.identifierb59011282en
dc.identifier.urihttp://hdl.handle.net/2152/1164en
dc.descriptiontexten
dc.description.abstractIt is estimated that more than 1/3 of the compounds being developed by the pharmaceutical industry are poorly water soluble. The bioavailability of these drugs is limited by their low dissolution rates. Two nanoparticle engineering processes, evaporative precipitation into aqueous solution (EPAS) and antisolvent precipitation were developed to enhance the dissolution rate of poorly water soluble drugs. EPAS is a process by which a drug solution in a water immiscible organic solvent is sprayed through an atomizer into an aqueous solution containing hydrophilic stabilizer (s) at high temperature. The rapid evaporation of the small organic droplets results in fast nucleation leading to submicron to micron particles suspensions. The adsorption of water soluble stabilizers on the drug particle surfaces facilitates the dissolution rates of the final powder after drying. The suspensions may be used in parenteral formulations to enhance bioavailability or may be dried to produce oral dosage forms with high dissolution rates due to small particle size and hydrophilic stabilizer that enhances wetting. The influence of EPAS process parameters on the physicochemical properties of poorly water soluble drugs was determined. The influence of the dissociation of drug molecules on the stability of nanosuspensions at high suspension concentration, as high as 30 mg/ml with a drug-to-surfactant ratio of 3:1, was investigated. High-potency (≥ 90%) drug particles with high dissolution rates were produced by removing the non-adsorbed surfactant. Antisolvent precipitation is a technique where a drug solution in a water miscible organic solvent is mixed with an aqueous solution containing a surfactant(s). Upon mixing, the supersaturated solution leads to nucleation and growth of drug particles, which may be stabilized by surfactants. Temperature was shown to have a large effect on the particle size distribution in the suspension. Crystalline drug particles with particle size of 300 nm were successfully recovered from the nanosuspensions by salt flocculation followed by filtration and vacuum drying with a drug yield higher than 92%. Upon redispersion, the average particle size was comparable to the value in the original aqueous suspension. The dissolution rate was correlated with the particle size after redispersion.
dc.format.mediumelectronicen
dc.language.isoengen
dc.rightsCopyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.en
dc.subject.lcshDrugs--Solubilityen
dc.subject.lcshNanoparticlesen
dc.titleNanoparticle engineering processes: evaporative precipitation into aqueous solution (EPAS) and antisolvent precipitation to enhance the dissolution rates of poorly water soluble drugsen
dc.description.departmentChemical Engineeringen
dc.identifier.oclc57551130en
dc.identifier.proqst3142708en
dc.type.genreThesisen
thesis.degree.departmentChemical Engineeringen
thesis.degree.disciplineChemical Engineeringen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen


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